Identification of a new class of small molecule C5a receptor antagonists
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- 作者：Jack J. Chen ; Derek C. Cole ; Greg Ciszewski ; Kimberly Crouse ; John W. Ellingboe ; Pawel Nowak ; Gregory J. Tawa ; Gabriel Berstein ; Wei Li
- 关键词：Anaphylatoxin ; C5a ; G-protein coupled receptor ; Anti-inflammation ; Autoimmune diseases
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2010
- 出版时间：15 January 2010
- 年：2010
- 卷：20
- 期：2
- 页码：662-664
- 全文大小：335 K
文摘
C5a is a terminal product of the complement cascade that activates and attracts inflammatory cells including granulocytes, mast cells and macrophages via a specific GPCR, the C5a receptor (C5aR). Inhibition of C5a/C5aR interaction has been shown to be efficacious in several animal models of autoimmune diseases, including RA, SLE and asthma. This account reports the discovery of a new class of C5aR antagonists through high-throughput screening. The lead compounds in this series are selective and block C5a binding, C5a-promoted calcium flux in human neutrophils with nanomolar potency.